The pentapeptide known as methionine-enkephalin is one of a family of peptides isolated from brain and pituitary extracts which are able to bind specifically to brain opiate receptors and which appear to be derived from the C-terminal portion of Beta-lipotropin. It seems that one or more of these compounds are components of a central pain suppressive system, particularly since several of them exert analgesic effects when injected into the brain. The object of this research is to carry out the synthesis and evaluate some biological and behavioral properties of Met-enkephalin analogs. In this way, we hope to elucidate the mechanism of action of the opiates and to develop analogs with increased analgesic activity, particularly after peripheral administration, decreased addictive properties, and fewer side-effects. The examination of analogs in several assay systems has revealed the presence of more than one receptor population and has opened up the way to designing peptides with increased specificity of action. Attempts are also being made to produce analogs which are devoid of analgesic activity but which are still able to bind to receptor sites and thus act as competitive inhibitors of endogenous opiates. The possibility obviously exists of developing anatgonists which are more specific for a particular class of receptors. Analog studies are also proceeding on the C61-91 fragment of Beta-LPH, Beta-endorphin. More efficient and economical synthetic methods are being developed. Basic studies on the effects of the opiate peptides on gastrointestinal processes are proceeding.